Follow-up of the GHSG HD16 trial of PET-guided treatment in early-stage favorable Hodgkin lymphoma.

The primary analysis of the GHSG HD16 trial indicated a significant loss of tumor control with PET-guided omission of radiotherapy (RT) in patients with early-stage favorable Hodgkin lymphoma (HL). This analysis reports long-term outcomes. Overall, 1150 patients aged 18-75 years with newly diagnosed early-stage favorable HL were randomized between standard combined-modality treatment (CMT) (2x ABVD followed by PET/CT [PET-2] and 20 Gy involved-field RT) and PET-2-guided treatment omitting RT in case of PET-2 negativity (Deauville score [DS] < 3). The study aimed at excluding inferiority of PET-2-guided treatment and assessing the prognostic impact of PET-2 in patients receiving CMT. At a median follow-up of 64 months, PET-2-negative patients had a 5-year progression-free survival (PFS) of 94.2% after CMT (n = 328) and 86.7% after ABVD alone (n = 300; HR = 2.05 [1.20-3.51]; p = 0.0072). 5-year OS was 98.3% and 98.8%, respectively (p = 0.14); 4/12 documented deaths were caused by second primary malignancies and only one by HL. Among patients assigned to CMT, 5-year PFS was better in PET-2-negative (n = 353; 94.0%) than in PET-2-positive patients (n = 340; 90.3%; p = 0.012). The difference was more pronounced when using DS4 as cut-off (DS 1-3: n = 571; 94.0% vs. DS ≥ 4: n = 122; 83.6%; p < 0.0001). Taken together, CMT should be considered standard treatment for early-stage favorable HL irrespective of the PET-2-result

Synergetic Effects of Granulocyte-Colony Stimulating Factor and Cognitive Training on Spatial Learning and Survival of Newborn Hippocampal Neurons

Granulocyte-Colony Stimulating Factor (G-CSF) is an endogenous hematopoietic growth factor known for its role in the proliferation and differentiation of cells of the myeloic lineage. Only recently its significance in the CNS has been uncovered. G-CSF attenuates apoptosis and controls proliferation and differentiation of neural stem cells. G-CSF activates upstream kinases of the cAMP response element binding protein (CREB), which is thought to facilitate the survival of neuronal precursors and to recruit new neurons into the dentate gyrus. CREB is also essential for spatial long-term memory formation. To assess the role and the potential of this factor on learning and memory-formation we systemically administered G-CSF in rats engaged in spatial learning in an eight-arm radial maze. G-CSF significantly improved spatial learning and increased in combination with cognitive training the survival of newborn neurons in the hippocampus as measured by bromodeoxyuridine and doublecortin immunohistochemistry. Additionally, G-CSF improved re-acquisition of spatial information after 26 days. These findings support the hypothesis that G-CSF can enhance learning and memory formation. Due to its easy applicability and its history as a well-tolerated hematological drug, the use of G-CSF opens up new neurological treatment opportunities in conditions where learning and memory-formation deficits occur

Quantitative assessment of F-18-FDG PET in patients with Hodgkin lymphoma: is it significantly affected by contrast-enhanced computed tomography attenuation correction?

Objective The reliability of visual and quantitative response assessment may be impaired owing to inconsistent scanning protocols and image reconstruction methods of 2-deoxy-2-[F-18]fluoro-d-glucose (F-18-FDG) PET. Hence, this study investigates the effect of contrast-enhanced computed tomography (CT) attenuation correction in patients with Hodgkin lymphoma. Patients and methods In 10 consecutive patients undergoing either staging or response assessment, F-18-FDG PET images were attenuation-corrected once on the basis of unenhanced CT and additionally using contrast-enhanced CT. Reconstruction was performed in both cases with ordered subset expectation maximization (OSEM) and ultra-high definition (UHD) algorithm. While maximum and peak standardized uptake value (SUV) were obtained from tumour tissue (lesionSUV(max) and lesionSUV(peak)), maximum and mean SUVs were determined within the background regions liver (liverSUV(max) and liverSUV(mean)) and mediastinal blood pool (mbpSUV(max) and mbpSUV(mean)). Results After switching to contrast-enhanced CT attenuation correction, lesionSUV(max) and lesionSUV(peak) increased on average by 2.55 +/- 3.24 (P=0.018) and 3.64 +/- 3.22% (P=0.008), respectively, with OSEM and by 4.59 +/- 5.49 (P=0.005) and 3.84 +/- 5.65% (P=0.005), respectively, with UHD reconstruction. LiverSUV(max) and liverSUV(mean) showed a mean rise of 7.15 +/- 4.27 (P=0.005) and 6.97 +/- 2.18% (P=0.005), respectively, in the OSEM data sets and of 7.24 +/- 6.59 (P=0.017) and 6.29 +/- 2.83% (P=0.005), respectively, in the UHD images. The average increases of mbpSUV(max) and mbpSUV(mean) were 10.82 +/- 4.89 (P=0.005) and 12.40 +/- 3.73% (P=0.005), respectively, after OSEM, compared with 13.11 +/- 14.93 (P=0.005) and 11.50 +/- 12.19% (P=0.005), respectively, after UHD reconstruction. Conclusion As the use of CT contrast fluids results in a stronger SUV increase within the liver and mediastinal blood pool than within lymphoma tissue, this may have clinical consequences regarding visual and quantitative response assessment. Ideally, CT scans for PET attenuation correction should therefore be performed in the absence of a contrast agent

Impact of PET/CT image reconstruction methods and liver uptake normalization strategies on quantitative image analysis (vol 43, pg 249, 2016)

Background In oncological imaging using PET/CT, the standardized uptake value has become the most common parameter used to measure tracer accumulation. The aim of this analysis was to evaluate ultra high definition (UHD) and ordered subset expectation maximization (OSEM) PET/CT reconstructions for their potential impact on quantification. Patients and methods We analyzed 40 PET/CT scans of lung cancer patients who had undergone PET/CT. Standardized uptake values corrected for body weight (SUV) and lean body mass (SUL) were determined in the single hottest lesion in the lung and normalized to the liver for UHD and OSEM reconstruction. Quantitative uptake values and their normalized ratios for the two reconstruction settings were compared using the Wilcoxon test. The distribution of quantitative uptake values and their ratios in relation to the reconstruction method used were demonstrated in the form of frequency distribution curves, box-plots and scatter plots. The agreement between OSEM and UHD reconstructions was assessed through Bland-Altman analysis. Results A significant difference was observed after OSEM and UHD reconstruction for SUV and SUL data tested (p <0.0005 in all cases). The mean values of the ratios after OSEM and UHD reconstruction showed equally significant differences (p <0.0005 in all cases). Bland-Altman analysis showed that the SUV and SUL and their normalized values were, on average, up to 60 % higher after UHD reconstruction as compared to OSEM reconstruction. Conclusion OSEM and HD reconstruction brought a significant difference for SUV and SUL, which remained constantly high after normalization to the liver, indicating that standardization of reconstruction and the use of comparable SUV measurements are crucial when using PET/CT